Nonlinear optical characterization of pharmaceutical formulations

Abstract

Abstract Unique challenges in formulating the next generation of active pharmaceutical ingredients (APIs) into stable formulations demand analytical tools not currently available using common benchtop methods. Herein, we review approaches to address some of these challenges through leveraging nonlinear optical (NLO) interactions between light and matter. Applications in dissolution testing, polymorphism, and accelerated stability testing highlight the breadth of these methods. The specificity of second harmonic generation (SHG) to chiral crystals supports rapid polymorphism analysis at the limit of individual crystals and informs formulations designs to address solubility challenges common in emerging drug candidates. Coherent anti-Stokes Raman spectroscopy (CARS) and stimulated Raman spectroscopy (SRS) provide vibration-specific microscopy of final dosage forms to inform composition at video-rate acquisition speeds and ∼1 μm spatial resolution. Recent results are reviewed to illustrate challenges in designing formulations for emerging drug candidates and opportunities for the development of NLO tools tailored to meet them.